The proposed program relates to the synthesis of 13C multilabeled cholesterol and Beta-sitosterol as potential diagnostic agents. Hypercholesterolemia has been implicated as a primary risk factor in coronary heart disease yet major questions regarding cholesterol absorption, transport, reverse transport and disposition remain to be elucidated for lack of a safe, convenient non-radioactive tracer methodology. Thus, stable isotope labeled dietary sterols in clinical protocols, combined with mass fragmentography, can be expected to aid the elaboration of indeces for such parameters as sterol pool size, transit time, volume distribution and clearance. The synthetic approach requires disconnection at C-22 of the sterol side chain and resynthesis with the labels positioned in the isopropyl terminus at (C-25, 26 and 27), the latter being derived from 13C3-acetone. Included among the project tasks are development of pathways conservative towards isotope and optimization of yields to provide multigram quantities of both sterols in seven synthetic steps. Yields in the 10-20% range are expected. Additionally, the program calls for development of an A-ring degradation and resynthesis via the Robinson annelation to give 13C4-labeled sterols. A repertory of various incrementally labeled A and/or chain labeled sterols can then be envisioned for application in simultaneous studies by multiple routes of tracer administration.